Guidance for manufacturers and Notified Bodies on ...

1 NBOG's Best Practice Guide applicable for AIMDD, MDD, and IVDD 2014-3. Guidance for manufacturers and Notified Bodies on reporting of design Changes and Changes of the Quality System 1 Introduction The Medical Devices Directives require certain changes of the device or of the quality system to be Notified to the Notified Body. The requirements differ slightly from directive to directive and from conformity assessment annex to conformity assessment annex. The following table with horizontal criteria for notification , criteria for a new approval and criteria to be assessed and, vertically the conformity assessment annexes shows the require- ments of the various annexes of the medical device directive (details for directives 90/385/EEC. and 98/79/EC see Appendix 1): Conformity Criteria for notification Criteria for a new Criteria to be assessment annex (supplementary) assessed approval 93/42 Annex II Any changes made to Changes could affect Conformity with the section the approved design conformity with the requirements of the essential require- directive ments 93/42 Annex III Any significant Changes may affect Conformity with the section 6 change made to the conformity with the provisions of this approved product essential require- directive ments or with the conditions prescribed for use of the product 93/42 Annex II Any plan for Requirements section substantial changes referred to in Annex 3.

2 To the quality system section or the product range covered 93/42 Annex V any plan for Requirements section substantial changes referred to in Section to the quality system 93/42 Annex VI any plan for Requirements section substantial changes referred to in Section to the quality system Despite the fact that the wordings are slightly differing between the various product specific annexes, the authorities assume that in all cases only those changes need to be Notified which could affect conformity with the essential requirements . If this is the case, there is also a need for a further approval. Thus the criterion on when a change notification has to take place is identical to the criterion on whether a further approval is needed. The criterion for approving the NBOG BPG 2014-3 Page 1 of 19. NBOG's Best Practice Guide 2014-3. change of the device is evidently the fulfilment of Essential Requirements applicable to the re- spective device and whether corresponding documentation has been updated correctly.

3 For the quality system annexes, the criteria for triggering a notification obligation are compa- rable. Basically, a notification is needed where there is a substantial change to the quality system. In all these cases the Notified Body has to act. The Notified Body has (a) to decide whether the changed quality system still fulfils the requirements of the respective conformity assessment annex. It is to be noted that these requirements are differing amongst the conformity assessment annexes. Accordingly, the Notified Body needs to dif- ferentiate between these Annexes when assessing which change might affect the fulfilment of the various requirements;. (b) also to assess whether changes to the quality system could affect the fulfilment of Essential Requirements by the devices manufactured under the quality system. 2 Definitions Supplier [1]. Organisation or person that provides a product, a service or information, and which is outside of the QMS of the manufacturer.

4 Examples of supplier: Producer, distributor, retailer or vendor of a product, or provider of a ser- vice or information For the purpose of this document, the product' supplied may be a process', a supplier may provide a sterilisation process. Note 1: For the purpose of this document, Note 1 of EN ISO 9000 does not apply Note 2: The term supplier may refer to a contractor' or subcontractor'. For the purposes of the document the terms are regarded as synonymous. Subcontractor See Note 2. Critical supplier A critical supplier is a supplier delivering materials, components, or services that may influence the safety or performance of the device [2]. Note In Commission Recommendation 2013/473/EU of 24 September 2013 on the audits and assessments performed by Notified Bodies in the field of medical devices instead of critical also the term crucial is used: subcontractors in charge of processes which are essential for ensuring compliance with legal requirements ( critical subcontractor') or a supplier of crucial components or of the entire devices (both: crucial supplier').

5 3 Steps of the manufacturer for the change assessment procedure The manufacturer shall have documented the responsibilities and authorities throughout imple- mentation of changes and have documented procedures and evidence for Need/wish to change the device, quality system or product range covered by the quality system Verification and validation to take the decision to effectively modify the product or the product range or the quality system related to its risk management process NBOG BPG 2014-3 Page 2 of 19. NBOG's Best Practice Guide 2014-3. The need to update the technical documentation Definition of a change implementation plan to monitor the change stages and meet the regulatory requirements Determination whether the change is substantial or not Decision to implement the change taken and the timing of implementation (dependent on Notified Body review). Information given to the Notified Body about any substantial change Final implementation of the change.

6 It is recommended that manufacturers contact and discuss with their Notified Body about any questions related to the substantial or not substantial characteristic of the change in order to get a common understanding. The manufacturer shall establish, maintain and apply a procedure for categorising and imple- menting any changes to the device design /type (including software) and/or quality system and/or product range as either substantial or not substantial. The reporting system of the manufacturer for substantial changes must fulfil the subsequent criteria: The manufacturer shall inform the Notified Body of the planned substantial changes as soon as possible without delay. A notification of any substantial change in the design /devices as well as in the quality system shall include A brief description of the modifications compared to the approved design /devices or the approved quality system The reason and origin for the changes/modifications In the case of design /device changes, a statement on the relevance to the compliance with the essential requirements The technical data and documentation supporting above points.

7 manufacturers shall maintain a current listing of devices covered by the certificate and update the Notified Body accordingly (see also [3]). 4 Steps of Notified Body for the change assessment procedure The Notified Body shall have documented the responsibilities and authorities for each individual change process. It must be clear who has taken the various decisions once a planned change comes to the notice of the Notified Body. Furthermore, the Notified Body must have documented procedures in place and operating. These shall sufficiently specify the Notified Body's assessment (complete/partial on desk/site ). These procedures shall also cover the verification of the manufacturer's imple- mentation of the following processes: Identification of a need/wish to change the device, quality system or product range covered by the quality system Determination whether the change is substantial or not Information given by the manufacturer to the Notified Body about any substantial change NBOG BPG 2014-3 Page 3 of 19.

8 NBOG's Best Practice Guide 2014-3. Verification and validation performed by the manufacturer to take the decision to effectively modify the product or the product range or the quality system related to its risk management process Definition of a change implementation plan to monitor the change stages and meet the regulatory requirements Decision to implement the change taken by the manufacturer and the timing of implementation (dependent on Notified Body review). The review by the Notified Body of the manufacturer s procedures (documentation and imple- mentation) to define a change (substantial or not) and to inform the Notified Body is a required part of the initial, surveillance and renewal audits of the quality system. The Notified Body has to check the manufacturer's procedure(s) for categorising, reporting and implementing any changes to the device design /type (including software) and/or quality system and/or product range as either substantial or not substantial.

9 Note: For quality system annexes the Notified Body shall on a sampling basis within its surveillance audits also review those changes considered by the manufacturer as non- substantial and which therefore have not been reported. Where a substantial change is reported, the Notified Body shall define the appropriate action including: Contract review Update of the contract if needed Document assessment related to the product or complete re-assessment of the design dossier or the type examination dossier Document assessment related to the quality system, special audit or complete re- assessment of the quality system Update of the EC certificate or addenda if needed List of elements for which implementation has to be checked during the next audit The Notified Body procedure is part of the assessment by the designating authority. 5 Criteria for substantial changes The manufacturer must report to the Notified Body any plan of substantial 1 changes before implementation.

10 In the different directives, the terminology used differs, substantial or significant . In this document only the term substantial is used. Product changes (Relates to directive 90/385/EEC Annex 2 section and Annex 3 section 6; directive 93/42/EEC Annex II section and Annex III section 6; directive 98/79/EC Annex III sec- tion , Annex IV section and and Annex V sections 6 and ). Product changes should be considered substantial if the change may affect The conformity with the essential requirements and/or The indications and/or contraindications and/or warnings determined by the manufacturer to be appropriate to ensure the clinical performance of the device. 1 For details and different wordings please see Appendix 2. NBOG BPG 2014-3 Page 4 of 19. NBOG's Best Practice Guide 2014-3. When determining whether or not a particular product change is substantial following con- siderations should be made (the list is not exhaustive): Changes of the intended purpose and/or the performance specification of the device?